Feasibility and Safety of Repeated Carbon Ion Radiotherapy for Locally Advanced Unresectable Pancreatic Cancer

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Abstract

Simple Summary

Despite the effectiveness of carbon ion radiotherapy (CIRT) for locally advanced unresectable pancreatic cancer (URPC), isolated local recurrence after CIRT is a therapeutic challenge. Herein, we aimed to evaluate the feasibility and safety of a second course of CIRT for locally recurrent URPC in 10 patients. One patient developed grade 3 diarrhea immediately after the second CIRT; no other grade 3 or higher adverse events were induced by CIRT. The estimated 1-year overall survival rate and local control rate after the second CIRT were 48% and 67%, respectively. Repeated CIRT is feasible with acceptable toxicity for selected patients with locally advanced URPC after CIRT.

Abstract

Purpose: The feasibility and safety of re-irradiation with carbon ion beams for locally recurrent unresectable pancreatic cancer (URPC) after carbon ion radiotherapy (CIRT) was evaluated. Methods: Medical records from patients with re-irradiated URPC who were treated with CIRT between November 2017 and February 2019 were reviewed. Inclusion criteria were (1) isolated local recurrence after CIRT, (2) URPC, and (3) tumor located at least 3 mm from the gastrointestinal tract. The first and second CIRT irradiation doses were 55.2 Gy (relative biological effectiveness) in 12 fractions. Results: Ten patients met the inclusion criteria. The median follow-up period was 25.5 months (range, 16.0–69.1) after the first CIRT and 8.9 months (range, 6.4–18.9) after the second CIRT. The median interval between the initial CIRT and the local recurrence was 15.8 months (range, 8.0–50.1). One patient developed grade 3 diarrhea immediately after the second CIRT; no other grade 3 or higher adverse events were attributed to CIRT. The estimated 1-year overall survival, local control, and progression-free survival rates after the second CIRT were 48%, 67%, and 34%, respectively. Conclusion: Repeated CIRT is feasible with acceptable toxicity for selected patients with locally advanced URPC after CIRT.

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Biophysical characteristics of HIMAC clinical irradiation system for heavy-ion radiation therapy

Shinichi Minohara, Masao Suzuki, Masahiro Endo … (1999)

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Reformulation of a clinical-dose system for carbon-ion radiotherapy treatment planning at the National Institute of Radiological Sciences, Japan.

Taku Inaniwa, Nobuyuki Kanematsu, Naruhiro Matsufuji … (2015)

At the National Institute of Radiological Sciences (NIRS), more than 8,000 patients have been treated for various tumors with carbon-ion (C-ion) radiotherapy in the past 20 years based on a radiobiologically defined clinical-dose system. Through clinical experience, including extensive dose escalation studies, optimum dose-fractionation protocols have been established for respective tumors, which may be considered as the standards in C-ion radiotherapy. Although the therapeutic appropriateness of the clinical-dose system has been widely demonstrated by clinical results, the system incorporates several oversimplifications such as dose-independent relative biological effectiveness (RBE), empirical nuclear fragmentation model, and use of dose-averaged linear energy transfer to represent the spectrum of particles. We took the opportunity to update the clinical-dose system at the time we started clinical treatment with pencil beam scanning, a new beam delivery method, in 2011. The requirements for the updated system were to correct the oversimplifications made in the original system, while harmonizing with the original system to maintain the established dose-fractionation protocols. In the updated system, the radiation quality of the therapeutic C-ion beam was derived with Monte Carlo simulations, and its biological effectiveness was predicted with a theoretical model. We selected the most used C-ion beam with αr = 0.764 Gy(-1) and β = 0.0615 Gy(-2) as reference radiation for RBE. The C-equivalent biological dose distribution is designed to allow the prescribed survival of tumor cells of the human salivary gland (HSG) in entire spread-out Bragg peak (SOBP) region, with consideration to the dose dependence of the RBE. This C-equivalent biological dose distribution is scaled to a clinical dose distribution to harmonize with our clinical experiences with C-ion radiotherapy. Treatment plans were made with the original and the updated clinical-dose systems, and both physical and clinical dose distributions were compared with regard to the prescribed dose level, beam energy, and SOBP width. Both systems provided uniform clinical dose distributions within the targets consistent with the prescriptions. The mean physical doses delivered to targets by the updated system agreed with the doses by the original system within ± 1.5% for all tested conditions. The updated system reflects the physical and biological characteristics of the therapeutic C-ion beam more accurately than the original system, while at the same time allowing the continued use of the dose-fractionation protocols established with the original system at NIRS.

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Effects of carbon ion beam on putative colon cancer stem cells and its comparison with X-rays.

Makoto Akashi, Ryuichi Okayasu, Yoshiya Furusawa … (2011)

Although carbon ion therapy facilities are expensive, the biological effects of carbon ion beam treatment may be better against cancer (and cancer stem cells) than the effects of a photon beam. To investigate whether a carbon ion beam may have a biological advantage over X-rays by targeting cancer stem-like cells, human colon cancer cells were used in vitro and in vivo. The in vitro relative biological effectiveness (RBE) values of a carbon ion beam relative to X-rays at the D10 values were from 1.63 to 1.74. Cancer stem-like CD133(+), CD44(+)/ESA(+) cells had a greater ability for colony and spheroid formation, as well as in vivo tumorigenicity compared with the CD133(-), CD44(-)/ESA(-) cells. FACS (fluorescence-activated cell sorting) data showed that cancer stem-like cells were more highly enriched after irradiation with X-rays than carbon ion at doses that produced the same level of biological efficacy. A colony assay for cancer stem-like cells showed that RBE values calculated by the D10 levels were from 2.05 to 2.28 for the carbon ion beam relative to X-rays. The in vivo xenotransplant assay showed an RBE of 3.05 to 3.25, calculated from the slope of the dose-response curve for tumor growth suppression. Carbon ion irradiation with 15 Gy induced more severe xenograft tumor cell cavitation and fibrosis without significant enhancement of cells with putative cancer stem cell markers, CD133, ESA, and CD44, compared with 30 Gy X-rays, and marker positive cells were significantly decreased following 30 Gy carbon ion irradiation. Taken together, carbon ion beam therapy may have an advantage over photon beam therapy by improved targeting of putative colon cancer stem-like cells. ©2011 AACR

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Author and article information

Contributors

Meritxell Arenas: Role: Academic Editor

Pierfrancesco Franco: Role: Academic Editor

Journal

Journal ID (nlm-ta): Cancers (Basel)

Journal ID (iso-abbrev): Cancers (Basel)

Journal ID (publisher-id): cancers

Title: Cancers

Publisher: MDPI

ISSN (Electronic): 2072-6694

Publication date (Electronic): 07 February 2021

Publication date Collection: February 2021

Volume: 13

Issue: 4

Electronic Location Identifier: 665

Affiliations

[1 ]Gunma University Heavy-ion Medical Center, Gunma University Graduate School of Medicine, Gunma 371-0811, Japan; shiba4885@ 123456yahoo.co.jp (S.S.); o_syohei_1015@ 123456yahoo.co.jp (S.O.); y.miyasaka@ 123456gunma-u.ac.jp (Y.M.); shibukei@ 123456gunma-u.ac.jp (K.S.); tohno@ 123456gunma-u.ac.jp (T.O.)

[2 ]Japanese Red Cross Maebashi Hospital, Gunma 371-0811, Japan; hiroki.kiyohara@ 123456maebashi.jrc.or.jp

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[* ]Correspondence: okamott@ 123456gunma-u.ac.jp

Author information

Masahiko Okamoto https://orcid.org/0000-0002-8787-3298

Shohei Okazaki https://orcid.org/0000-0001-6984-8454

Yuhei Miyasaka https://orcid.org/0000-0001-5137-1862

Tatsuya Ohno https://orcid.org/0000-0002-6703-3144

Article

Publisher ID: cancers-13-00665

DOI: 10.3390/cancers13040665

PMC ID: 7914638

PubMed ID: 33562274

SO-VID: 790d55e9-a2a9-4360-9bd9-01d09e34cf9c

License:

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

Feasibility and Safety of Repeated Carbon Ion Radiotherapy for Locally Advanced Unresectable Pancreatic Cancer

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Photoluminescent Nanomaterials

Most cited references 20

Biophysical characteristics of HIMAC clinical irradiation system for heavy-ion radiation therapy

Reformulation of a clinical-dose system for carbon-ion radiotherapy treatment planning at the National Institute of Radiological Sciences, Japan.

Effects of carbon ion beam on putative colon cancer stem cells and its comparison with X-rays.

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